异常认知衰老，包括痴呆症，在老龄人群中为健康和社会系统带来严重挑战。因此，表征与异常认知衰老相关的因素并制定必要的预防措施具有重要意义。载脂蛋白E基因 (APOE4) 的ε4等位基因已被广泛认可为晚发性阿尔茨海默病的遗传风险因素。APOE4携带者也更容易患心血管疾病，该疾病与认知功能损害的风险增加有关。另一方面，已发现APOE4与多种常见类型的癌症——这是一种主要的与年龄相关的疾病和导致死亡的主要原因——的发病风险降低有关。我们通过竞争风险模型首次研究了APOE4对认知衰退和死亡的相反影响，考虑到两种死亡方式：具有高量与低量经尸体解剖评估的阿尔茨海默病病理学。我们观察到，在具有低量阿尔茨海默型病理学的死亡人群中，APOE4与死亡风险降低有关；而在具有高量阿尔茨海默型病理学的死亡人群中，APOE4与死亡风险增加有关，而后者是认知功能损害的主要风险因素。文中还讨论了异常认知衰老的可能预防措施。© 2023. Springer Nature Limited.

Abnormal cognitive ageing, including dementia, poses serious challenges to health and social systems in ageing populations. As such, characterizing factors associated with abnormal cognitive ageing and developing needed preventive measures are of great importance. The ε4 allele of the Apolipoprotein E gene (APOE4) is a well-known genetic risk factor for late-onset Alzheimer's disease. APOE4 carriers are also at elevated risk of cardiovascular diseases which are associated with increased risk of cognitive impairment. On the other hand, APOE4 is known to be associated with reduced risk of multiple common types of cancer-a major age-related disease and leading cause of mortality. We conducted the first-ever study of APOE4's opposing effects on cognitive decline and mortality using competing risk models considering two types of death-death with high-amounts versus low-amounts of autopsy-assessed Alzheimer's neuropathology. We observed that APOE4 was associated with decreased mortality risk in people who died with low amounts of Alzheimer's-type neuropathology, but APOE4 was associated with increased mortality risk in people who died with high amounts of Alzheimer's-type neuropathology, a major risk factor of cognitive impairment. Possible preventive measures of abnormal cognitive ageing are also discussed.© 2023. Springer Nature Limited.